Many diseases that affect the human brain cannot be studied using animal models. In recent years new techniques have been developed in histology and molecular biology that can be applied to human post-mortem (autopsy) brain tissue. These studies have enabled neuroscientists to make significant advances in understanding the causes and mechanisms of many diseases that damage the brain. Further progress in these types of studies is dependent upon the continued supply of autopsy brain tissue. A human brain tissue resource center is being developed in the Neuropathology Unit at the University of Sydney. The aim of this important facility is to provide fresh-frozen and formalin fixed brain tissue to neuroscientists with an interest in alcohol- related disorders. Studies on dependence and tolerance, and mechanisms underlying structural changes in the brain are all feasible. New molecular biological techniques will also facilitate a range of genetic studies. Per capita consumption of alcohol in Australia is very high and alcohol-related brain damage is common. The principal investigator has been studying the long-term pathological effects of alcohol on the brain for 15 years and has collaborated in neuropharmacological, neurochemical and genetic studies. There are almost 3000 hospital and forensic autopsies per year in Sydney. One of the most important aspects of "brain banking" is the accuracy and reliability of clinical and pathological diagnoses. Clinical diagnoses are confirmed by interviews with local doctors, study of past hospital medical records, questionnaires to next-of-kin and by analysis of pathology, radiology and neuropsychology reports. Autopsy and toxicology findings are also important in deciding whether or not a case fulfills the strict criteria for banking. Cases are selected from Hospital and Forensic autopsies by the Principal Investigator and are transferred to the Neuropathology Unit in preparation for diagnostic neuropathology and banking. Half the brain is fixed in formalin and half is dessected and frozen at minus 80 degrees C. The formalin-fixed hemisphere is embedded in agarose and sliced into approximately sixty, 3mm thick, slices that are carefully examined and photographed. Photographs are digital and are burnt onto a CD for permanent storage and easy retrieval. They are used for measuring areas and volumes of regions of interest. Tissue blocks are taken from cerebral cortex, basal ganglia, thalamus and hypothalamus, cerebellum and brain-stem and are processed by embedding in wax. Thin (10mu) sections are cut, stained and mounted on glass slides for microscopic examination to identify abnormalities and exclude diseases such as Alzheimer's disease. Cases are coded for confidentiality and all clinical and pathological information is entered onto a data base. Expressions of interest will be sought from research groups, interested in obtaining material from the tissue resource center. Applications will be processed by a scientific review committee. Ethics approval from the parent Institution is mandatory. All collaborating groups must provide annual research reports and list publications arising from the work. A "bank" of this type is necessarily a long-term project and the maximum benefits will be seen as case numbers increase and subgroups of cases (eg males versus females) can be selectively studied.